Indanpentol derivatives

ABSTRACT

Compounds are provided having the structure ##STR1## wherein n is 1, 2 or 3, m is 0, 1 or 2, R 1 , R 2 , R 3 , R 4  and R 5  may be the same or different and can be hydrogen, lower alkyl, halo-lower alkyl, acyl, lower alkoxy-carbonyl ##STR2## amido ##STR3## or lower alkoxyalkylene, X is a straight or branched bivalent aliphatic radical and Y is ##STR4## These compounds are useful in the treatment of hypertension.

COMPOUNDS OF THE INVENTION

The present invention relates to indanyl, naphthyl and benzosuberanylderivatives which have a lowering effect on blood pressure and areuseful in the treatment of hypertension, in mammalian species, forexample, rats and dogs. In addition, the compounds of the invention canbe employed as antibiotics. A compound of formula I (below) as well asits physiologically acceptable acid salts may be compounded according topharmaceutical practice in oral or parenteral dosage forms such astablets, capsules, elixirs, injectables or powders for administration ofabout 100 mg. per day, preferably 125 mg. to 175 mg. per day, in 2 to 4divided doses.

Furthermore, the compounds of this invention are useful as watersofteners.

The compounds of the invention have the general formula: ##STR5##wherein n is 1, 2 or 3, m is 0, 1 or 2, R₁, R₂, R₃, R₄ and R₅ may be thesame or different and represent hydrogen, acyl, lower alkyl, halo-loweralkyl, lower alkoxy-carbonyl ##STR6## amido ##STR7## or loweralkoxyalkylene, R₆ is lower alkyl or monocyclic cycloalkyl, X is asingle bond or a straight or branched chain bivalent aliphatic radical,and Y is ##STR8## R₇ and R₈ may be the same or different, representinghydrogen, acyl, lower alkyl, halo-lower alkyl, monocyclic cycloalkyl,monocyclic cycloalkyl-loweralkyl, hydroxy-lower alkyl, monocyclic aryl,monocyclic aryl-lower alkyl, monocyclic heterocyclic.

The ##STR9## group may also form a heterocyclic radical.

X represents straight or branched chain bivalent aliphatic hydrocarbongroups having from zero to about ten carbon atoms, such as an alkylenegroup of the structure (CH₂)_(n), wherein n' is zero to ten, such asmethylene, ethylene, propylene, trimethylene, butylene,dimethylethylene, and the like. Furthermore, X can correspond to any ofthe lower alkyl groups exemplified hereinafter; R₁, R₂, R₃, R₄ and/or R₅and R₇ and/or R₈ may be an acyl radical of a hydrocarbon carboxylic acidof less than twelve carbon atoms, which may be exemplified by the loweralkanoic acids (e.g, formic, acetic, propionic, butyric, valeric,trimethyl acetic and caproic acids), the lower alkenoic acids (e.g.,acrylic, methacrylic, crotonic, 3-butenoic and senecioic acids), themonocyclic aryl-carboxylic acids (e.g., benzoic and toluic acids), themonocyclic aryl-lower alkanoic acids [e.g., phenacetic,β-phenylpropionic, α-phenylbutyric, and 5-(p-methylphenyl)pentanoicacids], the cycloalkyl carboxylic acids (e.g., cyclobutane carboxylicacid, cyclopentane carboxylic acid and cyclohexane carboxylic acid), thecycloalkenyl carboxylic acids (e.g., 2-cyclobutene carboxylic acid and3-cyclopentene carboxylic acid), the cycloalkyl and cycloalkenyl-loweralkanoic acids [e.g., cyclohexaneacetic, α-cyclopentanebutyric,2-cyclopenteneacetic and 3-(3-cyclohexane)pentenoic acid], and the like.

The alkanoic acids may include halogen substituents, for example,trifluoroacetic acid. In addition, other acyl groups which can beemployed are angeloyl, veratroyl, vanilloyl,erythro-2-hydroxy-2-methyl-3-acetoxybutyryl, (1)-2-methylbutyryl;(d)-2-hydroxy-2-methylbutyryl; (d)-threo-2,3-dihydroxy-2-methylbutyryland (1)-erythro-2,3-dihydroxy-2-methylbutyryl.

The term "lower alkyl" as employed herein includes both straight andbranched chain radicals of up to eight carbon atoms, for instance,methyl, ethyl, propyl, isopropyl, butyl, t-butyl, isobutyl, pentyl,hexyl, isohexyl, heptyl, 4,4-dimethylpentyl, octyl,2,2,4-trimethylpentyl, and the like.

Alkyl radicals substituted by F, Br, Cl or I are encompassed by the termhalo-lower alkyl. Trifluoromethyl is a preferred halo-lower alkylradical.

The term "monocyclic aryl" as employed herein contemplates monocycliccarbocyclic aryl radicals, for instance, phenyl and substituted phenylradicals, such as lower alkyl phenyl (e.g., o-, m- or p-tolyl,ethylphenyl, butylphenyl, and the like), di(lower alkyl)phenyl (e.g.,2,4-dimethylphenyl, 3,5-diethylphenyl, and the like), halophenyl (e.g.,chlorophenyl, bromophenyl, iodophenyl, fluorophenyl), o-, m- orp-nitrophenyl, dinitrophenyl, (e.g., 3,5-dinitrophenyl,2,6-dinitrophenyl, and the like), trinitrophenyl (e.g., picryl).

The term "monocyclic aryoyl" includes any of the above aryl groupslinked to a carbonyl group.

The term "monocyclic cycloalkyl" and "monocyclic cycloalkenyl" includescyclic radicals containing from 3 to 6 ring members (e.g., cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, cyclobutenyl and cyclohexenyl).

As indicated hereinbefore, ##STR10## may form a heterocyclic radical.The symbols R₇ and R₈ may together represent the carbon (and hydrogen)and the oxygen, sulfur or nitrogen atoms which, with the nitrogen orcarbon atoms in the above group, form a 5-, 6- or 7-membered nitrogenheterocyclic containing not more than one hetero atom in addition to thenitrogen already shown in the group and less than 21 atoms in theradical (excluding hydrogen). The heterocyclic radicals may include oneto three substituents including lower alkoxy or lower alkyl as definedhereinafter; trihalomethoxy, such as trifluoromethoxy;trihalomethylmercapto, such as trifluoromethylmercapto;N,N-dialkylsulfamoyl groups, such as N,N-dimethylsulfamoyl; loweralkanoyl groups as defined hereinafter such as acetyl, propionyl, andthe like; hydroxy; hydroxy-lower alkyl, such as hydroxymethyl,2-hydroxyethyl, or the like; hydroxy-lower alkoxy-lower alkyl, such as2-(2-hydroxyethoxy)ethyl, or the like; alkanoyloxy containing analkanoyl as defined herein; alkanoyloxy-lower alkyl (up to about 14carbons in the alkanoyl group), such as 2-heptanoyloxyethyl; carbo-loweralkoxy, such as carbomethoxy, carboethoxy, carbopropoxy, or the like; or2-(alkanoyloxy-lower alkoxy) lower alkyl (with up to about 14 carbons inthe alkanoyl group), such as 2-(decanoyloxyethoxy)-ethyl, or the like.

Illustrative of the heterocyclic radicals represented by R₇, R₈ or##STR11## are the following: piperidino; (lower alkyl)piperidino [e.g.,2-, 3-, or 4-(lower alkyl)-piperidino or 4-(N-lower alkyl)piperidinosuch as 2-(ethyl)-piperidino or 4-(N-isopropyl)-piperidino]; di(loweralkyl)-piperidino [e.g., 2,4-, 2,5- or 3,5-di(lower alkyl)piperidinosuch as 2,4-dimethylpiperidino or 2,5-di-t-butyl piperidino]; (loweralkoxy)piperidino [e.g., 2-methoxypiperdino or 3-methoxypiperidino];hydroxypiperidino [e.g., 3-hydroxy- or 4-hydroxypiperidino];aminomethylpiperidino [e.g., 4-aminomethylpiperidino]; pyrrolidino;(lower alkyl)pyrrolidino [e.g., 3-methylpyrrolidino]; di(loweralkyl)pyrrolidino [e.g., 3,4-dimethylpyrrolidino]; (loweralkoxy)pyrrolidino [e.g., 2-methoxypyrrolidino]; morpholino; (loweralkyl)-morpholino [e.g., 3-methylmorpholino]; di(lower alkyl)morpholino[e.g., 3,5- dimethylmorpholino]; (lower alkoxy)morpholino [e.g.,2-methoxymorpholino]; thiamorpholino; (lower alkyl)-thiamorpholino[e.g., 3-methylthiamorpholino]; di(lower alkyl)-thiamorpholino [e.g.,3,5-dimethylthiamorpholino; (lower alkoxy)thiamorpholino [e.g.,3-methoxythiamorpholino]; piperazino; (lower alkyl)piperazino [e.g., N⁴-methylpiperazino]; di(lower alkyl)piperazino [e.g.,2,5-dimethylpiperzino or 2,6-dimethylpiperazino]; (loweralkoxy)piperazino [e.g., 2-methoxypiperazino]; (hydroxy-loweralkyl)piperazino [e.g., N⁴ -(2-hydroxyethyl)piperazino];(alkanoyloxy-lower alkyl)piperazino wherein the alkanoyloxy group has upto 14 carbons [e.g., N⁴ -(2-heptanoyloxyethyl)piperazino or N⁴-(2-dodecanoyloxyethyl)piperazino]; (hydroxy-lower alkoxy-loweralkyl)piperazino [e.g., (hydroxy-methoxy-methyl)piperazino];(carbo-lower alkoxy)piperazino [e.g., N⁴ -(carbomethoxy-, carboethoxy-,or carbopropoxy)piperazino]; homopiperazino; or N⁴ -(hydroxy-loweralkyl)homopiperazino [e.g., N⁴ -(2-hydroxyethyl)homopiperazino];piperidyl; (lower alkyl)piperidyl [e.g., 1-, 2-, 3- or 4-(loweralkyl)piperidyl, such as 1-N-methylpiperidyl or 3-ethylpiperidyl];di(lower alkyl)-piperidyl [e.g., 2,4-, 2,5-, or 3,5-di(loweralkyl)piperidyl wherein lower alkyl is methyl, ethyl, n-propyl,isopropyl, etc.]; lower alkoxy piperidyl [e.g., 3-methoxypiperidyl or2-ethoxypiperidyl]; hydroxy piperidyl [e.g., 3-hydroxy- or4-hydroxypiperidyl]; aminomethylpiperidyl [e.g., 4-aminoethylpiperidyl];pyrrolidyl; lower alkyl pyrrolidyl [e.g., 1-N- methylpyrrolidyl];di(lower alkyl)pyrrolidyl [e.g., 2,3-dimethylpyrrolidyl]; lower alkoxypyrrolidyl [e.g., 4-N-methoxypyrrolidyl]; morpholinyl; (loweralkyl)morpholinyl [e.g., 3-methylmorpholinyl]; di(loweralkyl)morpholinyl [e.g., 3-methyl-4-N-ethylmorpholinyl]; (loweralkoxy)morpholinyl [e.g., 2-ethoxymorpholinyl]; thiamorpholinyl; (loweralkyl)thiamorpholinyl [e.g., 3-ethylthiamorpholinyl]; di(loweralkyl)thiamorpholinyl [e.g., 3-methyl-4-N-ethylthiamorpholinyl]; loweralkoxy thiamorpholino [e.g., 3-methoxythiamorpholinyl]; piperazinyl;alkyl, dialkyl, alkoxy or hydroxy-lower alkyl substituted piperazinyl.

The N-oxides of the compounds of formula I wherein Y represents anitrogen containing heterocyclic radical can be formed by reacting suchformula I compounds with a peracid such as m-chloroperoxy benzoic acid,perbenzoic acid or monoperphthalic acid in a suitable solvent such aschloroform.

The compounds of formula I form acid addition salts by reaction withvarious inorganic and organic acids. These salts frequently provideconvenient means for separating the product from the reaction mixture inwhich it is produced or from the solvent in which it is extracted inview of their insolubility in various media. Thus the product may beprecipitated in the form of an insoluble salt and converted, byconventional techniques, to the free base or to another soluble orinsoluble salt as desired.

Illustrative salts include the hydrohalides, such as hydrochloride,hydrobromide and hydroiodide, especially the first two, other mineralacid salts such as phosphate, sulfate, nitrate, etc., organic acid saltssuch as oxalate, tartrate, malate, maleate, citrate, pamoate, fumarate,camphorsulfonate, methanesulfonate, benzenesulfonate, toluenesulfonate,salicylate, benzoate, ascorbate, mandelate, or the like.

The compounds of formula I also form quaternary ammonium salts withlower alkyl halides, for example, methyl bromide, ethyl bromide andpropyl iodide; benzyl halides, such as benzyl chloride; and diloweralkyl sulfates, such as dimethyl sulfate. To form the quaternaryammonium salts, the free base initially formed is intereacted with atleast one equivalent of the desired alkylating agent.

Preferred are those compounds wherein n is 1 or 2, X is (CH₂)₂ or(CH₂)₃, Y is an amino group or a piperidino group with or withoutsubstituents, R₁, R₂, R₃, R₄ and R₅ are hydrogen or acyl and m is 0.Most preferred are those compounds wherein n is 1, X is (CH₂)₂ or(CH₂)₃, Y is dimethylamino or ##STR12##

In all of the compounds of the invention, the OR₁, OR₂, OR₃ and OR₄groups are axial and OR₁ and OR₂ are in trans configuration and OR₃ andOR₄ are in trans configuration.

The compounds of formula I includes all stereoisomers and mixturesthereof. Thus X-Y can be cis or trans to OR₃ and OR₅ can be cis or transto X-Y.

The compounds of Formula I of the invention may be prepared by a processwhich comprises forming a diene of the structure II. ##STR13## andconverting the diene to the pentol or pentol derivatives of Formula I.

The pentol wherein R₁, R₂, R₃, and R₄ are hydrogen, can be formed byhydroxylating the diene to the corresponding pentol, for example, byreacting the diene with formic acid and aqueous hydrogen peroxide, attemperatures ranging from about 20° to 40° C to form a mixture ofesters, and then subjecting the mixture of esters to basic hydrolysis bydissolving the mixture of esters in a solvent boiling below about 100°C, such as a monohydric alcohol containing up to four carbon atoms(e.g., methyl alcohol, ethyl alcohol, propyl alcohol, isopropyl alcoholor butyl alcohol), and then treating the solution with a base, such asan alkali metal of alkaline earth metal hydroxide or alkoxide (e.g.,sodium hydroxide, potassium hydroxide, barium hydroxide, calciumhydroxide, sodium methoxide or calcium diethoxide) and heating themixture to temperatures ranging from about 40° to about 80° C, to formthe pentol of the structure: ##STR14##

In the above reaction the hydrogen peroxide is employed in a molar ratioto the diene of within the range of from about 2.2:1 to about 15:1 andpreferably from about 2.2:1 to about 5:1. The base is employed in amolar ratio to the mixture of esters of within the range of from about2.2:1 to about 10:1 and preferably from about 2.2:1 to about 5:1.

The pentol of Formula III can be converted to the corresponding pentaester, i.e., where R₁, R₂, R₃, R₄ and R₅ are acyl as definedhereinbefore, by reacting the pentol with an acylating agent, such as ahydrocarbon carboxylic acid containing less than twelve carbon atoms asdiscussed hereinbefore, the acid anhydride thereof, or correspondingacyl halide, and an acid catalyst, such as perchloric acid, at atemperature within the range of from about -20° to about 0° C. The acid,acid anhydride or acyl halide is employed in a molar ratio to the pentolof within the range of from about 5:1 to about 20:1 and preferably fromabout 5:1 to about 10:1 and the acid catalyst is employed in a molarratio to the pentol of within the range of from about 1.1:1 to about 2:1and preferably about 1.1:1 to about 1.5:1.

In an alternative procedure, the diene of formula II can be converted tothe corresponding pentol by dissolving the diene II in an organiccarboxylic acid having up to about eight carbon atoms, such as aceticacid, treating the mixture with a silver salt corresponding to the acid,such as silver acetate (in a molar ratio of diene to silver salt ofwithin the range of from about 1:2 to about 1:4 and preferably about1:2) and iodine (in a molar ratio of diene to iodine of 1:1), heatingthe reaction mixture at a temperature of within the range of from about60° to about 110° and preferably from about 80° to about 100°, to form acompound (depending on which acid and silver salt are employed) of thestructure: ##STR15##

The above diester of the structure IV can be converted to thecorresponding pentol by dissolving the diester in a suitable protonicsolvent, such as ethyl alcohol, treating the solution with an excess ofan aqueous base, such as aqueous sodium hydroxide or potassiumhydroxide, to effect hydrolysis to the corresponding triol of thestructure: ##STR16##

The above triol can be converted to the pentol by reacting with formicacid and hydrogen peroxide (as described hereinbefore), at temperaturesranging from about 20° to about 40° C, preferably about 35°, and thentreating the mixture (free of solvent) with an alcohol and a base (asdescribed hereinbefore) to form the pentol wherein OR's (1 to 4) areaxial and each pair of OR's (1 and 2, and 3 and 4) are trans.

The pentols or derivatives thereof can also be prepared by reacting thediene II with formic acid and one equivalent of an oxidizing agent, suchas aqueous hydrogen peroxide, and after removal of solvent, dissolvingthe residue in an alcohol-base as described hereinbefore to effecthydrolysis and form a triol olefin of the structure: ##STR17## The abovetriol olefin can then be converted to the pentol as describedhereinbefore with respect to the conversion of the triol olefin V.

Where Y is ##STR18## and at least one of R₇ and R₈ is or includes anaromatic ring, the pentols of the invention can be prepared by reducinga hydroxyalkyl compound of the structure: ##STR19## wherein X is loweralkylene as defined hereinbefore with respect to the correspondingdiene, by reacting VII with a reducing metal, such as lithium or sodiumin liquid ammonia in the presence of a proton source such as a loweralcohol, to form the corresponding hydroxyalkyl diene of the structure:##STR20## dissolving the hydroxyalkyl diene in a basic organic solvent,such as pyridine, cooling the solution to below 0°, treating thesolution with a solution of p-toluene sulfonyl chloride in pyridine, ina molar ratio of diene to p-toluene sulfonyl chloride of within therange of from about 1:1 to about 1:1.5, and cooling to form thecorresponding diene tosylate of the structure ##STR21## reacting thediene tosylate with an arylamine or substituted arylamine, aryl loweralkylamine or substituted aryl lower alkylamine or an amine of thestructure ##STR22## (in a molar ratio of tosylate to amine of within therange of from about 1:2 to about 1:5) in an aromatic solvent boilingbelow about 120° C, such as toluene or benzene to form anaminoalkyldiene of the structure: ##STR23## wherein R'₇ and R'₈ are thesame or different and can be aryl, substituted aryl, arylalkyl,substituted arylalkyl or any of the R₇ and R₈ substitutents mentionedpreviously. The substituted aryl groups can include any of thesubstituents set out hereinbefore with respect to the heterocyclicgroups. The aminoalkyl diene can be converted to the correspondingpentol by reacting the diene with formic acid and an oxidizing agent,such as hydrogen peroxide, removing solvent and subjecting the residueto basic hydrolysis (alcohol-base) as described hereinbefore, to form apentol of the structure: wherein R'₇ and R'₈ are as defined above. WhenR'₇ or R'₈ is benzyl it can be converted to a hydrogen atom by treatingthe pentol with hydrogen in the presence of a catalyst for reduction,such as palladium on strontium carbonate.

Where Y is NH₂, the pentols of the invention can be prepared by reactingan aminoalkyl indene (prepared by reduction of the correspondingcyanoalkyl indene) or an aminoalkyl tetrahydronaphthalene with areducing agent, such as lithium ribbon in the presence of liquidammonia, ethyl ether, and a proton source such as a lower alcohol, toform a diene of the structure: ##STR24## and reacting the diene with anacyl halide (wherein acyl and the halogen are as defined hereinbefore),such as benzoyl chloride, in a molar ratio of diene:halide of within therange of from about 1:1 to about 2:1 in a basic solvent, such aspyridine, triethylamine, or dilute base to form a diene of the structure##STR25## and reacting the diene with formic acid and an oxidizingagent, such as hydrogen peroxide, and subjecting the product to basichydrolysis (as described hereinbefore) to form an aminoalkyl pentol ofthe structure: ##STR26##

The pentol tetraacylate of formula I, wherein R₅ is H, can be preparedfrom the diene alcohol X (or II) by conversion to the succinate halfester, A, using ##STR27## succinic anhydride in pyridine, convertingthis to a salt with a strong non-participating acid, such as perchloric,in a carboxylic acid, such as acetic, oxidizing with the peracid of thesame carboxylic acid, such as peracetic acid, in a ratio of peracid todiene of about 2:1 to about 3:1, precipitating the oxidation product byaddition of non-polar diluents, such as benzene and ethyl ether, andacylating the crude oxidation product with the addition of the samecarboxylic acid anhydride, such as acetic anhydride, to give, ondilution with ethyl ether, the tetra acyl succinate, B. ##STR28## Thetetraacyl succinate B can be converted to the pentol tetra acylate C bydissolving in an aqueous solution of ##STR29## a weak base, such assodium bicarbonate, and warming at temperatures from 40°-80° C for aperiod of from 15 minutes to 1 hour.

PREPARATION OF OTHER TETROL DERIVATIVES

The pentol ethers of formula I wherein R₁, R₂, R₃, R₄ and R₅ are loweralkyl can be prepared by dissolving a pentol of Formula I in a suitablenonprotonic solvent such as benzene, dioxane, ethyl ether ortetrahydrofuran, adding to the solution at least four equivalents andpreferably from about five to about seven equivalents of a metal hydridesuch as sodium hydride or sodium amide, thereafter adding to the mixtureslowly with stirring about five equivalents of a lower alkyl halide suchas methyl iodide, methyl bromide or ethyl iodide, and maintaining thetemperature of the reaction mixture within the range of from about 20°to about 60° C and preferably from about 30 to about 40° C, to form thetetrol ether. Thereafter, ethyl alcohol and/or water can be added todecompose excess base, and the tetrol ether can be recovered bystripping down the organic solvent.

Pentols of Formula I wherein R₁, R₂, R₃, R₄ and R₅ are halo-lower alkylcan be formed as described hereinbefore with respect to the preparationof the pentol ethers with the exception that an alkylene halohalide (ordihaloalkane) such as trimethylene chlorobromide or pentamethylenefluoro iodide, is employed in place of the alkyl halide.

Pentols of Formula I wherein R₁, R₂, R₃, R₄ and R₅ are dialkyl carbamylcan be found as described hereinbefore with respect to the preparationof the pentol ethers with the exception that a dialkyl carbamoyl halide,such as dimethyl carbamyl chloride or diethyl carbamoyl bromide, or asubstituted isocyanate such as an alkyl or aryl isocyanate is employedin place of the alkyl halide.

Pentols of Formula I wherein R₁, R₂, R₃, R₄ and R₅ are loweralkoxyalkylene wherein the alkylene group contains two to five carbonatoms can be formed as described hereinbefore with respect to thepreparation of the pentol ethers except that an alkoxyalkylene halidesuch as ethoxypropyl chloride or ethoxyethyl bromide is employed inplace of the alkyl halide.

Pentols of Formula I wherein R₁, R₂, R₃, R₄ and R₅ are ##STR30## can beformed as described hereinbefore with respect to the preparation of thepentol ethers except that an alkylhaloformate such asmethylchloroformate or ethylchloroformate is employed in place of thealkyl halide.

Alternative Methods for Preparing Indanyl, Naphthyl and BenzosuberanylDerivatives

The dienes of the structure ##STR31## are novel intermediates.

The triol olefins of the structure VI that is ##STR32## wherein X and Yare defined hereinbefore are novel intermediates.

Triol olefins of the structure VI correspond to the pentols and estersand the triester and triol olefins of structures IV and V set outhereinbefore.

The diene intermediate II, when n=l, ##STR33## can be prepared byreacting a starting material of the structure ##STR34## with an alkyleneoxide and a strong base such as butyl-lithium or butyl-sodium in asolvent such as ethyl ether to form the hydroxyalkyl compound of thestructure, ##STR35## dissolving the hydroxyalkyl compound in a basicorganic solvent, such as pyridine, cooling the solution to below 0°,treating the solution with a solution of p-toluene sulfonyl chloride inpyridine, in a molar ratio of hydroxyalkyl compound to p-toluenesulfonyl chloride of within the range of from about 1:1 to about 1:1.5,and cooling to form the corresponding tosylate of the structure,##STR36## reacting the tosylate with an amine of the structure ##STR37##in a molar ratio of tosylate to amine of within the range of from about1:2 to about 1:5, in an aromatic solvent boiling below about 120° C,such as toluene or benzene, to form an aminoalkylene compound of thestructure ##STR38## Thereafter, the aminoalkylene compound can besubjected to hydroboration of the double bond by reaction with diborane.The reaction mixture is then subjected to oxidation by treating withalkali metal hydroxide and hydrogen peroxide to form a compound of thestructure which is reduced by reaction with a reducing agent, such aslithium ribbon in the presence of liquid ammonia, ethyl ether and aproton source such as a lower alcohol, to form a diene of the structureII, when n=1. Alternatively, the diene intermediate II, when n=1, can beprepared by reacting a starting material such as XVIII with an alkyldihalide, such as 1,3-dibromo propane, and a strong base such as TritonB and a metal hydroxide, in water, to form the haloalkyl compound of thestructure ##STR39## reacting the halide with an amine of the structurein a molar ratio of halide to amine of within the range of from about1:2 to about 1:5, in an aromatic solvent boiling below about 120° C,such as toluene or benzene, to form an aminoalkylene compound of thestructure ##STR40## which can be reacted as was XXI to give XXII.

The diene intermediate II, when n=1, 2 or 3, ##STR41## can be preparedstarting with the ketone shown below. ##STR42## Reaction of the ketonewith an aminoalkyl Grignard reagent followed by acid catalyzeddehydration yields the amino alkylene compound ##STR43## The reactionsequence of hydroboration and oxidation with alkaline hydrogen peroxideyields the intermediate ##STR44## which is reduced as with XXII to thediene II.

Dienes of the structure II may alternatively be prepared by formicacid-hydrogen peroxide hydroxylation of the double bond conjugated tothe aromatic ring in a compound of the structure ##STR45## to form adiol, which on acid treatment forms the ketone. ##STR46## This isreduced by reaction with a complex metal hydride to form the alcoholXXIV which is reduced as above.

The following examples illustrate the present invention without,however, limiting the same thereto. All temperatures are expressed indegrees Centigrade.

EXAMPLE 12,3-trans-4a,8a-trans-5-[3-(Dimethylamino)propyl]-decahydro-2,3,4a,6,8a-naphthalenepentolA. 1-Dimethylaminopropyl-3,4-dihydronaphthalene

The Grignard reagent from 300 g (2.5 moles) of dimethylaminopropylchloride and 60 g (2.5 moles) of magnesium turnings is prepared in 2 l.of tetrahydrofuran. To this is added 300 g (2.0 moles) of α-tetralone in1 l. of tetrahydrofuran, at a rate to maintain reflux. After theaddition the reflux is continued for 1.5 hours, then the mixture iscooled in ice and quenched with 500 ml of saturated ammonium chloride.The layers are separated, and the aqueous diluted with water andreextracted with ether. The organics are evaporated, then treated with amixture of 350 ml of concentrated HCl and 1400 ml of glacial acetic acidat reflux for 1/2 hour. The solvents are removed in vacuo, and theresidue taken up in water, and the aqueous extracted with benzene.Basification liberates the product which is extracted with benzene,dried over carbonate, the solvent evaporated, and the product distilledat 129° C, 0.3 mmHg to give 250 g (58%) of a light yellow liquid,1-dimethylaminopropyl-3,4-dihydronaphthalene.

B.1,2-trans-1-[3-(Dimethylamino)propyl]-1,2,3,4,5,8-hexahydro-2-naphthol

A solution of 1-dimethylaminopropyl-3,4-dihydronaphthalene (43 g) in 300ml of tetrahydrofuran is treated over 45 minutes with 400 ml of 1Mborane solution in tetrahydrofuran at 0° C under nitrogen. The mixtureis warmed to 25° C for 1 hour, then cooled to 0° C and treated with 60ml of water by drops, 340 ml of 10% sodium hydroxide, and finally 75 mlof 30% hydrogen peroxide over 15 minutes. After stirring 1 hour at0°-15° C the mixture is diluted to 2 liters with water, the layersseparated, and the aqueous extracted with 1.5 liters of chloroform.Drying (sodium sulfate) and evaporation gives an oil which is refluxed 1hour in a mixture of 600 ml of 95% ethanol and 600 ml of 5% HC1. Another600 ml of water is added and ethanol evaporated in vacuo. The resultingaqueous phase is extracted with chloroform (discard), basified (10%caustic) and extracted with chloroform (1 liter). The organics are dried(sodium sulfate), 500 ml of benzene is added, and the mixture evaporatedto give 43 g (93%) of the 2-hydroxy compound, largely a single spot onTLC, chloroform, neutral alumina.

The above amino alcohol (43 g, 0.18 mole) in 300 ml of ether is added to2 liters of ammonia, treated with 35 g (5 moles) of lithium, stirred 1hour, and treated with absolute ethanol over 3 hours to discharge theblue color. The ammonia is evaporated overnight, and water and ether areadded with ice cooling. The aqueous phase is reextracted with ether, theorganics dried (potassium carbonate), benzene added, and evaporated togive 38 g (87%) of1,2-trans-1-[(dimethylamino)propyl[-1,2,3,4,5,8-hexahydro-2-naphthol.

C.2,3-trans-4a,8a-trans-5-[3-(Dimethylamino)propyl]-decahydro-2,3,4a,6,8a-naphthalenepentol

A solution of 33 g (0.l4 mole) of the free base formed in part B in 1liter of 88% formic acid is treated over 5 minutes with 40 ml (0.35mole) of 30% hydrogen peroxide, T < 38° C. with cooling. After 31/2 daysat room temperature the mixture is evaporated to an oil, taken up in 500ml of 95% ethanol, basified with 10% sodium hydroxide and heated for 1hour on a steam cone. Cooling, extraction with ether and ethyl acetateuntil the organics are colorless, drying (magnesium sulfate) andevaporation with added benzene gives 27 g of an oil. This is taken up in300 ml of acetonitrile and 100 ml of ethyl acetate, and diluted whilehot with 600 ml of benzene. Cooling and occasional scratching give aftertwo days 9.0 g (21%) of crude2,3-trans-4a,8a-trans-5-[3-(dimethylamino)propyl]-decahydro-2,3,4a,6,8a-naphthalenepentol,m.p. 123°-129° C.

A 1.7 g sample of pentol is crystallized after Darco treatment from 60ml of ethyl acetate. The crystals are crushed and dried at 80° C over P₂O₅ and paraffin at 0.1 mm Hg for two days to give 1.2 g, m.p. 140°-143°C.

EXAMPLE 22,3-trans-4a,8a-trans-5-[3-(Dimethylamino)propyl]decahydro-2,3,4a,6,8a-naphthalenepentol,pentaacetate ester

A 3.0 g (0.01 mole) sample of2,3-trans-4a,8a-trans-5-[3-(dimethylamino)propyl]-decahydro-2,3,4a,6,8a-naphthalenepentol(prepared as in Example 1) is slurried in 100 ml of acetic anhydride,cooled in a Dry Ice-acetone bath and treated with 3 ml of 70% perchloricacid. After standing at -15° C. overnight the mixture is cooled inice-acetone and treated dropwise with 70 ml of methanol. The solution ispoured into a mixture of ice and concentrated ammonium hydroxide,extracted with ether and chloroform, the combined extracts dried(magnesium sulfate) and evaporated with added benzene to give 4.6 g(90%) crude solid 2,3-trans-4a,8a-trans-5[3-(dimethylamino)propyl]decahydro-2,3,4a,6,8a-naphthalenepentol,pentaacetate ester.

Recrystallization from 225 ml of 2:1 hexane:ethyl acetate with Darcotreatment and drying for 24 hours at 140° C over P₂ O₅ and paraffin at0.1 mm Hg give 1.8 g, m.p. 201°-206° C.

EXAMPLE 32,3-trans-4a,8a-trans-5-[3-(Dimethylamino)propyl]-decahydro-2,3,4a,6,8a-naphthalenepentol,pentaacetate ester (Isomer of the product of Example 2)

A 30.4 g (0.14 mole) sample of1-(3-dimethylaminopropyl)-3,4-dihydronaphthalene (prepared as in Example1A) is taken up in 350 ml of 97% formic acid and treated while stillwarm with 13.2 ml of 30% hydrogen peroxide, T ≦ 50° C, with cooling.After standing overnight the mixture is stripped to an oil, then takenup in 300 ml of 5% sulfuric acid and heated on a steam cone for 1 hour.The mixture is cooled, basified with 10% sodium hydroxide and extractedwith chloroform, the organics dried overnight at 5° C over sodiumsulfate. Evaporation affords 16 g (44%) of crude product. This is takenup in 300 ml of dichloromethane and added to a slurry of 14 g of lithiumaluminum hydride in 400 ml of ether. This mixture is refluxed 1 hour,then quenched with ethyl acetate and finally water. Filtration andevaporation affords 9 g (59%) oily product. This material (0.036 mole)is submitted to Birch reduction using 10 g (1.5 mole) lithium, 500 ml ofammonia and 100 ml of ether to give 4.5 g (56%) of oily hydroxydiene.This material (0.02 mole) is oxidized with 10 ml of 30% hydrogenperoxide in 200 ml of 97% formic acid. After 18 hours, the mixture isstripped, hydrolyzed in ethanolic sodium hydroxide, extracted with ethylacetate, dried (magnesium sulfate) and stripped to an oil with benzeneadded to remove water. The oil is triturated with hexane, and theresidue taken up in 100 ml of acetic anhydride and 10 ml of acetic acid,and the peracetylation at -15° C. catalyzed with 3.5 ml of 70%perchloric acid. Workup, by using 70 ml of methanol gives an oil showingvery weak hydroxyl absorption in the infrared spectrum. This is boiledin 150 ml of hexane until no more dissolved. Decanting and coolingovernight gives 2 g (20%) of crude pentaacetate. This is taken up indichloromethane (40 ml), hexane added and boiled until thedichloromethane is removed (volume = 100 ml). Standing at roomtemperature overnight gives 0.4 g, m.p. 178°-195° C. The mother liquoris concentrated on a steam cone to 40 ml, cooled to 25° C and scratched.Filtering in 3 hours gives 0.6 g of2,3-trans-4a,8a-trans-5-[3-(dimethylamino)propyl]decahyro-2,3,4a,6,8a-naphthalenepentol,pentaacetate ester, m.p. 156°-163° C.

EXAMPLE 4 3a,7a-trans-5,6-trans-1-[3-(Dimethylamino)propyl]hexahydro2,3a,5,6,7a-indanpentol A. trans-1-[3-(Dimethylamino)propyl]-2-indanol

A solution of 20.6 g (0.10 mole) of 1-[3-(dimethylamino)-propyl]-indenein 100 ml of tetrahydrofuran is coold to 0° under nitrogen and 200 ml of1M borane in tetrahydrofuran added over 30 minutes. After stirringovernight at ambient temperature the solution is cooled to 0° and thefollowing added in the given order: 30 ml of water added cautiously, 170ml of 10% sodium hydroxide solution and 32 ml of 30% hydrogen peroxidesolution. After 1 hour at 0° the mixture is diluted with 1 liter ofwater and extracted with chloroform (3 × 400 ml) to give a white solidwhich is refluxed with 300 ml each of ethanol and 5% hydrochloric acidfor 1 hour. After addition of 300 ml of water, 400 ml of distillate iscollected. The residue is cooled, extracted with chloroform (200 ml,discard), basified with excess sodium hydroxide and extracted withchloroform (3 × 300 ml). Drying and solvent removal give 17.6 g of oil(81%, 1 spot on TLC).

3a,7a-trans-5,6-trans-1-[3-(Dimethylamino)propyl]-hexahydro-2,3a,5,6,7a-indanpentol,hydrochloride

trans-1-[3-(Dimethylamino)propyl]-2-indanol (13.9 g, 0.054 mole) isdissolved in a mixture of 100 ml of tetrahydrofuran and 1 liter ofliquid ammonia. Over 40 minutes, 17.5 g (2.5 g-atom) of lithium is addedfollowed by 220 ml of ethanol over 195 minutes. The ammonia isevaporated and the residue poured into 1 liter of ice-water andextracted with chloroform (3 × 500 ml). Drying and solvent removal gives13.1 g of oil with negligible UV absorption at 250-300 Mμ (2.2 × 10⁻³M).

This oil is dissolved in 130 ml of cold 98% formic acid and thetemperature brought to 24°. Over 10 minutes, 12 ml of 30% hydrogenperoxide is added and the temperature kept at 40° with a cold waterbath. After 30 minutes the temperature begins to fall and the mixture isstirred for 3 days at ambient temperature. The formic acid is removed invacuo and the residue refluxed for 1 hour with 100 ml of ethanol, 100 mlof water and 30 g of sodium hydroxide. After cooling, the mixture isextracted with ether (8 × 150 ml) and chloroform-methanol (19:1) to give3.1 and 0.4 g of dark oil, respectively. (TLC shows 5 major components).

The aqueous solution is diluted with water, concentrated to 150 ml andthe sodium hydroxide neutralized by passing gaseous carbon dioxidethrough the solution. A dark oil forms which is mechanically separated,taken up in 5% methanol in chloroform, dried over magnesium sulfate andevaporated to give 5.3 g of heavy oil which resists crystallization.Conversion to the hydrochloride and recrystallization three times fromisopropanol give 1.65 g, m.p. 190°-195° dec.

The mother liquors are combined and the volume reduced to give, in twocrops, 1.50 g of tan powder, m.p. 179°-185° dec.

EXAMPLE 53a,7a-trans-5,6-trans-1-[3-(dimethylamino)propyl]hexahydro2,3a,5,6,7a-indanpentol,pentaacetate ester

A slurry of 1.50 g (0.0046 mole) of3a,7a-trans-5,6-trans-1-[3-(dimethylamino)propyl]-hexahydro-2,3a,5,6,7a-indanpentol(prepared as in Example 4) in 60 ml of acetic anhydride is cooled to dryice-acetone temperature and 1.0 ml of 70% perchloric acid added. Thesolid dissolves as the temperature is raised to -20°. After storingovernight at -15°, 30 ml of methanol is added at <-10°,and the resultingsolution partitioned between 100 ml of cold concentrated ammoniumhydroxide and 200 ml of ether. The ether layer is separated, washed withwater, saturated salt solution and dried. Solvent removal gives 1.83 gof oil which solidifies and is recrystallized twice from ca. 8/2 -hexane/ethyl acetate to give 1.19 g, m.p. 137.5°-145.5°.

EXAMPLE 61,2-trans-3a,7a-trans-5,6-trans-Hexahydro-1-(2-piperidinoethyl)-2,3a,5,6,7a-indanpentolA. 2-(1-Indenyl)ethanol

The above compound is prepared as described by Howell & Taylor, J.C.S.,1957, 3013. To butyl-lithium, prepared from lithium (20.0 g) and butylbromide (234 g) in ether, indene (116 g., 1.0 M) is added with stirringunder nitrogen at -10°. After 1 hour at -10°, ethylene oxide (88 g) inether (300 ml) is added in 1/2 hour. After warming to 10°, 500 ml wateris added cautiously and stirring is continued until there is no lithiumremaining. The layers are separated and the organic layer is washed oncewith dilute HCl and three times with water. After drying the ether isremoved and the product distilled - collecting 76 g (48%) at 125-135/0.2mm. N.M.R. establishes the position of the double bond as 2,3.

B. 2-(1-Indenyl)ethyl tosylate

The alcohol prepared as described above in part A (49 g, 0.306 M) ismixed with 64.8 g (0.350 M) p-toluenesulfonyl chloride. The paste iscooled to 0° and pyridine (49 g, 0.62 M) is added dropwise over a periodof one hour. The cold solution is stirred for four hours before anexcess of dilute HCl is added. The product is extracted with etheryielding 95 g (99+%) viscous tosylate. N.M.R. establishes the positionof the double bond as 2,3.

C. 1-[2-(3-Indenyl)ethyl]piperidine

The crude tosylate prepared as described in part B above (41.5 g, 0.13M) and piperidine (28 g, 0.33 M) in 200 ml toluene are heated underreflux overnight. Ether is added to the warm reaction mixture untilcrystals begin forming. After cooling, the solid is removed byfiltration and washed several times with ether. The filtrate and washesare combined and the solvents removed in vacuo. The oily residue isdissolved in ether, a small amount of insoluble material is removed byfiltration, and the ether is removed from the filtrate leaving 29.7 g(99%) of brown oil. The sample is purified by distillation at reducedpressure recovering 86% as a yellow oil boiling 115°/0.05 mm. to130°/0.1 mm.

D. 1-(2-Piperidinoethyl)-2-indanol

The 1-[2-(3-indenyl)ethyl]piperidine compound prepared as describedabove in part C is hydroborated with diborane generated in situ. Theindenyl compound (20.4 g, 0.09 M) and sodium borohydride (9.0 g, 0.22 M)are dissolved in 300 ml of diglyme which has been purified bydistillation from lithium aluminum hydride. The system is swept withnitrogen and cooled in an ice bath. A solution of boron trifluorideetherate (50.4 g, 0.36 M) in diglyme (60 ml) is added dropwise over aperiod of one hour, maintaining the temperature at 5°-7° C. Thistemperature is held 1 hour after addition then left 2 hours at roomtemperature.

The excess hydride is decomposed by cautious addition of 20 ml water.The mixture is then oxidized by addition of 75 ml of 6 N NaOH anddropwise addition (1 hour) of 150 ml 30% hydrogen peroxide. Two hoursafter addition is complete the mixture is filtered, acidified withdilute HCl, and the solvent is removed in vacuo heating to ˜ 70° C. Theyellow solid which remains is dissolved in water, basified with solid K₂CO₃, and the product is extracted with benzene giving 18.5 g crudealcohol. This is dissolved in ether, converted to the hydrochloridewhich is filtered off (16.3 g, 64%, melting 197°-200°).

The hydrochloride is dissolved in water, basified with NaOH and the freebase is extracted with ether. After removal of the ether 13.1 g of oilremains (60%).

E.1,2-trans-3a,7a-trans-5,6-trans-Hexahydro-1-(2-piperidinoethyl)-2,3a,5,6,7a-indanpentol

A solution of the 1-(2-piperidinoethyl)-2-indanol prepared as describedabove in part D (13.1 g, 0.053 M) in 100 ml ether is added to 1 l.liquid ammonia and 100 ml ether. Lithium ribbon (20.0 g, 2.85 M) isadded in several portions over a period of 15 minutes while stirring.The bluish-bronze mixture is stirred 11/2 hours. Absolute ethanol isadded dropwise until the blue color is discharged (300 ml is required,added over a period of 2 hours). The ammonia is evaporated, the residueis diluted to 1500 ml with water and extracted three times with ether.The ether extracts are dried over magnesium sulfate and the ether isremoved in vacuo leaving 13.5 g amber oil. Comparison of the IR and UVof the product with those of the starting material indicates no startingmaterial remains.

The oil (0.053 M) is added dropwise over a period of 15 minutes to 100ml cold 98% formic acid. This is followed by dropwise addition (30minutes) of 57 g (˜ 0.5 M) 30% hydrogen peroxide maintaining atemperature of 20° C. The temperature is then allowed to rise to 35° andis held at 30°-35°, using a large water bath, for three hours before itis left stirring overnight. The reaction mixture is taken to neardryness and any residual performic acid is removed by twice adding waterand removing in vacuo.

The remaining yellow oil is dissolved in 100 ml absolute ethanol. Asolution of 30 g KOH in 50 ml water is added. The mixture, which darkensimmediately, is heated under reflux one hour. After cooling, the mixtureis diluted to 500 ml with water. This is extracted three times withether (yield: 3.4 g), two times with chloroform (yield: 2.4 g) andfinally three times with i-amyl alcohol (yield: 8.0 g). Total materialextracted: 13.8 g (77%). The extracts are crystallized separately frommethanolacetone. First crop materials (3.5 g combined) have similarmelting points and identical IR's. They are combined and purified byrecrystallization from methanolacetone to give 2.2 g (12%) m.p.223°-226° C.

EXAMPLE 73a,7a-trans-5,6-trans-Hexahydro-1-(3-piperidinopropyl)-2,3a,5,6,7a-indanpentol,hydrochloride 3-(3'-Bromopropyl)indene

The compound is prepared as described by Makoska in Tetrahedron Letters38, 4261-4624 (1966) by adding a mixture of 580 g (5M) indene and 1010 g(5M) 1,3-dibromopropane to 1500 ml 50% aqueous NaOH containing 50 ml 40%methanolic Triton B. The temperature is held below 55° C by cooling inan ice bath. After stirring 6 hours the reaction mixture is diluted to 4l. The layers are separated and the aqueous layer is extracted two timeswith ether. The combined organic layers are extracted two times withwater, dried over MgSO₄, filtered and the solvent is removed. The oilyproduct is distilled and redistilled at reduced pressure collecting 432g (36.6%) boiling 126°-140°/0.1 mm.

B. 1-[3-(3-Indenyl)propyl]piperidine

3-(3'-Bromopropyl)indene (94.8 g, 0.4 M) and piperidine (76 g, 0.9 M)are dissolved in 400 ml toluene. The mixture is heated under reflux 2hours. After cooling, a large amount of solid is removed by filtrationand washed with ether. The combined filtrate and washes are concentratedin vacuo. The residue is dissolved in ether and filtered to remove asmall amount of insoluble material. The ether is removed in vacuo andthe product is distilled collecting a fraction of 87.3 g (89% yield)boiling 132°-153°/0.05 mm.

C. 1-(3-Piperidinopropyl)-2-indanol

1-[3-(3-Indenyl)propyl]piperidine (48.2 g, 0.2 M) is dissolved in 400 mltetrahydrofuran and stirred in a nitrogen atmosphere while 400 ml 1Mborane in tetrahydrofuran is added dropwise over a period of 1 hour. Themixture is left stirring overnight at room temperature. Most of thesolvent is then removed in vacuo. The viscous residue is dissolved in500 ml 95% ethanol, treated with 20 g NaOH and then 65 ml of 30% H₂ O₂is added dropwise over a period of 30 minutes. The mixture is stirred atroom temperature for 2 hours and then heated under reflux for 21/2hours. The mixture is then taken to near dryness in vacuo. The residueis then extracted three times with benzene. The benzene extracts aredried, filtered and the solvent is removed in vacuo leaving 57 g of oil.The VPC of this material indicates ˜ 97% purity.

D. 4,7-Dihydro-1-(3-piperidinopropyl)-2-indanol

The crude 1-(3-piperidinopropyl)-2-indanol (˜ 0.2 M) is dissolved in 300ml ether and added to 2 liters liquid ammonia. Lithium ribbon (50 g) isadded in small portions over a period of 30 minutes. After stirring 11/2hours, absolute ethanol is added dropwise until the color is discharged(˜ 1 liter added over a period of 4 hours). The ammonia is allowed toevaporate and the residue is then diluted to 4 liters with water; twoether extracts yield 62 g of crude diene which becomes partiallycrystalline on standing.

E.3a,7a-trans-5,6-trans-Hexahydro-1-(3-piperidinopropyl)-2,3a,5,6,7a-indanpentol,hydrochloride

Crude 4,7-dihydro-1-(3-piperidinopropyl)-2-indanol (prepared asdescribed in part C) (˜ 0.19 M) is added slowly to 300 ml cold 98%formic acid. Hydrogen peroxide (175 ml of 30%) is then added dropwiseover a period of 45 minutes maintaining a temperature of 20°-25° C. Thetemperature is then allowed to rise to 35° and is held at 30°-35°, usinga large water bath, for three hours before the mixture is left stirringovernight. Water (50 ml) is added and excess peroxide is decomposed byadding sodium sulfite. The solvent is removed in vacuo.

The viscous residue is dissolved in 400 ml 95% ethanol and treated witha solution of 90 g KOH in 100 ml water. The dark mixture is heated underreflux 1 hour, cooled, and diluted to 1 liter with water. Four etherextracts yield 41.4 g and four ethyl acetate extractions yield anadditional 9.3 g. Only 2 g is obtained partially crystalline (this fromethyl acetate extracts). The remaining material is chromatographed onActivity IV basic alumina. Elution with 5 and 10% methanol in chloroformgive fractions containing 29.4 g of material. This material is dissolvedin ethyl acetate and after standing 15.9 g of crude3a,7a-trans-5,6-trans-hexahydro-1-(3-piperidinopropyl)-2,3a,5,6,7a-indanpentolis removed by filtration (total solid 17.9 g, 29% yield).

A 4 g sample of the crude pentol is converted to the hydrochloride byreacting the same with hydrochloric acid. Three recrystallization fromisopropyl alcohol-ethanol yield 1.5 g (˜ 34%), m.p. 215° (dec).

EXAMPLE 83a,7a-trans-5,6-trans-Hexahydro-1-(3-piperidinopropyl)-2,3a,5,6,7a-indanpentol,pentaacetate ester

Crude3a,7a-trans-5,6-trans-hexahydro-1-(3-piperidinopropyl)-2,3a,5,6,7a-indanpentol(3.0 g, 0.0091M) (prepared as described in Example 7) is partiallydissolved in 60 ml acetic anhydride and 2 ml acetic acid. While coolingto -30° C, 4.5 ml 70% HClO₄ dropwise is added over a period of 15minutes. The mixture is kept at -15° for 22 hours; solid precipitatesduring this time. Cooling is continued during dropwise addition ofmethanol (30 ml); the mixture is then poured into 100 ml coldconcentrated NH₄ OH, and extracted two times with chloroform. Thechloroform extract are dried over MgSO₄, filtered, and the solvent isremoved in vacuo leaving 5.28 g of yellow foam. Two recrystallizationsfrom hexane containing a small amount of ether yield 3.7 g (76%) m.p.121°-140° C.

EXAMPLE 9 3a,7a-trans-5,6-trans-Hexahydro-1-[3-(trans-3-hydroxy-4-methylpiperidino)propyl]-2,3a,5,6,7a-indanpentol,hydrochloride A. 1 -[3-(3-Indenyl)propyl]-4-methylpyridinium bromide

A solution of 121 g (0.51 mole) of 3-(3-bromopropyl)indene (prepared asin Example 7) and 68 g (0.74 mole) of γ-picoline in 150 ml ofacetonitrile is heated at reflux temperature overnight. A small amountof ether is added and the mixture let stand at room temperature for 3hours, and then filtered. The solid collected is washed with ether anddried in vacuo to give 138 g (0.419 mole) of tan solid, mp 93°-123°.

B. 1,2,3,6-Tetrahydro-1-[3-(3-indenyl)propyl]-4-methylpyridine,hydrochloride

A solution of 135 g (0.409 mole) of the compound formed in part A abovein 200 ml of water and 120 ml of methanol is cooled to 15°. Over aperiod of 30 minutes, 16 g (0.424 mole) of sodium borohydride is added.The mixture is stirred for 2 hours at room temperature, acidified withglacial acetic acid, and then basified with potassium carbonate. It isextracted with a total of 1200 ml of ethyl ether (containing 200 ml ofchloroform) and 600 ml of chloroform. All organic extracts are combined,dried and evaporated in vacuo to give 129 g of an orange-brown liquid.

A chloroform solution of this material is extracted with 1 liter of 7%hydrochloric acid which is separated, basified and extracted with ether.The ether extract is dried and evaporated to give 19 g of black sludgewhich is discarded. The original chloroform layer is evaporated in vacuoto give 140 g of dense oil whose IR spectrum indicates that it is ahydrochloride salt. This material is slurried with ether, basified andthe ether layer dried and evaporated to give 82 g of mobile oil which isdistilled in vacuo to give, after a forerun of 5.7 g, bp 130-151° at 0.4mm, 41.3 g of oil, bp 146-156° at 0.4 mm.

C. trans,trans-1-[3-(3-Hydroxy-4-methylpiperidino)propyl]-2-indanol,hydrochloride

A solution of 41.26 g (0.16 mole) of1,2,3,6-tetrahydro-1-[3-(3-indenyl)propyl]-4-methylpyridine (as the freebase) in 350 ml of tetrahydrofuran is cooled to 10°, and 340 ml of 7Mborane in tetrahydrofuran (0.34 mole) is added over 25 minutes. Themixture is stirred overnight at room temperature, cooled to 0° and 40 mlof water is added carefully. A solution of 30 g of sodium hydroxide in270 ml of H₂ O is added followed by 70 ml of 30% hydrogen peroxide over25 minutes. The mixture is stirred at room temperature for 1 hour andthen the layers separated. The aqueous phase is washed twice with ether,and then all organic extracts are combined, washed with saturated sodiumchloride solution, dried over sodium sulfate and evaporated in vacuo togive 62 g of dense oil. This is dissolved in a solution of 100 ml ofconcentrated hydrochloric acid, 500 ml of ethanol and 400 ml of waterand the mixture refluxed for 1 hour. Approximately 500 ml of solvent isdistilled out and the remaining solution is cooled and extracted withchloroform (discard). The aqueous layer is separated, basified and thenextracted with a total of 1 liter of chloroform which is dried andevaporated in vacuo to give 53.2 g of dense oil having the above name.

D.trans-4,7-Dihydro-1-[3-(trans-3-hydroxy-4-methyl-piperidino)propyl]-2-indanol

A solution of 44 g (0.15 mole) oftrans,trans-1-[3-hydroxy-4-methylpiperidino)propyl]-2-indanol (preparedas described in part D) (as the free base) in 150 ml of ether, 100 ml oftetrahydrofuran and ca. 1.5 l of liquid ammonia is prepared and 26.8 g(3.84 g-atoms) of lithium added over 70 minutes. The mixture is stirredat reflux for 30 minutes, 260 ml of absolute ethanol is added over 45minutes, and the ammonia evaporated. The residue is partitioned between900 ml of cold water and 600 ml of ether. The aqueous layer is washedwith 2 × 300 ml of ether. The ether extracts are combined, washed withsaturated sodium chloride solution, dried and evaporated in vacuo togive 45.2 g of dense oil (100%).

E.3a,7a-trans-5,6-trans-Hexahydro-1-[3-(trans-3-hydroxy-4-methylpiperidino)propyl]-2,3a,5,6,7a-indanpentol,hydrochloride

An amount of 38 ml of 30% hydrogen peroxide is added over 45 minutes toa solution of 45 g oftrans-4,7-dihydro-1-[3-(trans-3-hydroxy-4-methylpiperidino)propyl]-2-indanolprepared as in part B) in 400 ml of 98% formic acid. The mixture isstirred at room temperature for 64 hours, diluted with water andevaporated in vacuo twice to give an oil which is refluxed with 150 mlof 95% ethanol, 84 g potassium hydroxide and 350 ml of water for 1.5hour. The mixture is cooled and extracted with 5% methanol in chloroformto give 8.3 g of foam (15.2%) which by TLC contains hexol contaminatedby several impurities. The aqueous layer is extracted with a total of3.2 liters of ethyl acetate to give 9.05 g of solid (16.6%). A 6.05 gportion of this solid is dissolved in isopropanol, the hydrochloridesalt prepared and recrystallized twice from isopropanol/methanol/etherto a white solid, 1.3 g, m.p. 223°-224° (19.6%), and a pale yellowsolid, 1.39 g (20.9%).

Example 10 3a,7a-trans-5,6-trans-Hexahydro-1-[3-(trans-3-hydroxy-4-methylpiperidino)propyl]-2,3a,5,6,7a-indanpentol,hexaacetate ester

A slurry of 2 g (0.005 mole) of3a,7a-trans-5,6-trans-hexahydro-1-[3-(trans-3-hydroxy-4-methylpiperidino)propyl]-2,3a,5,6,7a-indanpentol(prepared as described in Example 9) in 40 ml of acetic anhydride and1.5 ml of glacial acetic acid is cooled in a dry ice-acetone bath, 1.5ml of 70% perchloric acid added dropwise and the solution stored 16hours at -20°. The solution is cooled to -15°, 30 ml of methanol addedand the solution poured into 100 ml of cold concentrated ammoniumhydroxide. This mixture is extracted with a total of 800 ml of ether,which is washed with saturated sodium chloride, dried, and evaporated invacuo to give 2.7 g foam (88.5%). This is recrystallized twice fromhexane/ethyl acetate to give a white solid, 1.36 g m.p. 117.5°-125°.

Examples 11 to 56

Following the procedure of Example 6 but substituting for indene thecompound listed in Column I of Table I set out below, and substitutingfor piperidine the compound listed in Column II, the compound listed inColumn II is obtained.

                                      TABLE I                                     __________________________________________________________________________    Ex.                                                                           No.                                                                              Column I       Column II      Column III                                   __________________________________________________________________________     ##STR47##                                                                                                      ##STR48##                                       R.sub.6 (position)                                                                      m                                                                                  ##STR49##      R.sub.6 (position)                                                                      m                                                                                ##STR50##                      __________________________________________________________________________       H         --   HN(C.sub.2 H.sub.5).sub.2                                                                    H         -- N(C.sub.2 H.sub.5).sub.2           H         --                                                                                  ##STR51##     H         --                                                                                ##STR52##                         H         --   NH.sub.3       H         -- NH.sub.2                           H         --   HNHCH.sub.3    H         -- NHCH.sub.3                         H         --                                                                                  ##STR53##     H         --                                                                                ##STR54##                         H         --                                                                                  ##STR55##     H         --                                                                                ##STR56##                         H         --                                                                                  ##STR57##     H         --                                                                                ##STR58##                         H         --                                                                                  ##STR59##     H         --                                                                                ##STR60##                         H         --                                                                                  ##STR61##     H         --                                                                                ##STR62##                      20.                                                                              C.sub.2 H.sub.5 (2)                                                                     1                                                                                   ##STR63##     C.sub.2 H.sub.5 (2)                                                                     1                                                                                 ##STR64##                         CH.sub.3 (1)                                                                            1                                                                                   ##STR65##     CH.sub.3 (1)                                                                            1                                                                                 ##STR66##                          ##STR67##                                                                              1    HN(CH.sub.3).sub.2                                                                            ##STR68##                                                                              1  N(CH.sub.3).sub.2                  H         --                                                                                  ##STR69##     H         --                                                                                ##STR70##                         H         --   HN(CH.sub.2 Cl).sub.2                                                                        H         -- N(CH.sub.2 Cl).sub.2               H         --                                                                                  ##STR71##     H         --                                                                                ##STR72##                         H         --                                                                                  ##STR73##     H         --                                                                                ##STR74##                         di-CH.sub.3 (1,2)                                                                       2                                                                                   ##STR75##     di-CH.sub.3 (1,2)                                                                       2                                                                                 ##STR76##                         C.sub.3 H.sub.7 (3)                                                                     1    HN(C.sub.6 H.sub.5).sub.2                                                                    C.sub.3 H.sub.7 (3)                                                                     1  N(C.sub.6 H.sub.5).sub.2           H         --                                                                                  ##STR77##     H         --                                                                                ##STR78##                      30.                                                                              H         --   HN(CH.sub.2 C.sub.6 H.sub.5).sub.2                                                           H         -- N(CH.sub.2 C.sub.6 H.sub.5).                                                  sub.2                              CH.sub.3 (2), C.sub.2 H.sub.5 (3)                                                       2                                                                                   ##STR79##     CH.sub.3 (2), C.sub.2 H.sub.5                                                           23)                                                                               ##STR80##                         H         --   HN(CH.sub.2 CH.sub.2 OH).sub.2                                                               H         -- N(CH.sub.2 CH.sub.2                                                           OH).sub.2                          H         --                                                                                  ##STR81##     H         --                                                                                ##STR82##                       ##STR83##                                                                                                      ##STR84##                                       R.sub.6 (position)                                                                      m                                                                                  ##STR85##      R.sub.6 (position)                                                                      m                                                                                ##STR86##                      __________________________________________________________________________       H         --   HN(C.sub.2 H.sub.5).sub.2                                                                    H         -- N(C.sub.2 H.sub.5).sub.2           H         --                                                                                  ##STR87##     H         --                                                                                ##STR88##                         H         --   NH.sub.3       H         -- NH.sub.2                           H         --   HNHCH.sub.3    H         -- NHCH.sub.3                         C.sub.2 H.sub.5 (1)                                                                     1                                                                                   ##STR89##     C.sub.2 H.sub.5 (1)                                                                     1                                                                                 ##STR90##                         H         --                                                                                  ##STR91##     H         --                                                                                ##STR92##                      40.                                                                              CH.sub.3 (2)                                                                            1                                                                                   ##STR93##     CH.sub.3 (2)                                                                            1                                                                                 ##STR94##                         H         --                                                                                  ##STR95##     H         --                                                                                ##STR96##                         di-C.sub.2 H.sub.5 (1,2)                                                                2                                                                                   ##STR97##     di-C.sub.2 H.sub.5 (1,2)                                                                2                                                                                 ##STR98##                         C.sub.2 H.sub.5 (2)                                                                     1                                                                                   ##STR99##     C.sub.2 H.sub.5 (2)                                                                     1                                                                                 ##STR100##                      ##STR101##                                                                                                     ##STR102##                                      R.sub.6 (position)                                                                      m                                                                                  ##STR103##     R.sub.6 (position)                                                                      m                                                                                ##STR104##                     __________________________________________________________________________       CH.sub.3 (1)                                                                            1                                                                                   ##STR105##    CH.sub.3 (1)                                                                            1                                                                                 ##STR106##                         ##STR107##                                                                             1    HN(CH.sub.3).sub.2                                                                            ##STR108##                                                                             1  N(CH.sub.3).sub.2                  H         --                                                                                  ##STR109##    H         --                                                                                ##STR110##                        H         --   HN(CH.sub.2 Cl).sub.2                                                                        H         -- N(CH.sub.2 Cl).sub.2               H         --                                                                                  ##STR111##    H         --                                                                                ##STR112##                        H         --                                                                                  ##STR113##    H         --                                                                                ##STR114##                     50.                                                                              CH.sub.3 (2)                                                                            1                                                                                   ##STR115##    CH.sub.3 (2)                                                                            1                                                                                 ##STR116##                        C.sub.3 H.sub.7 (3)                                                                     1    HN(C.sub.6 H.sub.5).sub.2                                                                    C.sub.3 H.sub.7 (3)                                                                     1  N(C.sub.6 H.sub.5).sub.2           H         --                                                                                  ##STR117##    H         --                                                                                ##STR118##                        H         --   HN(CH.sub.2 C.sub.6 H.sub.5).sub.2                                                           H         -- N(CH.sub.2 C.sub.6 H.sub.5).                                                  sub.2                              H         --                                                                                  ##STR119##    H         --                                                                                ##STR120##                        H         --   HN(CH.sub.2 CH.sub.2 OH).sub.2                                                               H         -- N(CH.sub.2 CH.sub.2                                                           OH).sub.2                          H         --                                                                                  ##STR121##    H         --                                                                                ##STR122##                     __________________________________________________________________________

examples 57 to 102

Following the procedure of Example 8, but substituting for the3a,7a-trans-5,6-trans-hexahydro-1-(3-piperidinopropyl)-2,3a,5,6,7a-indanpentolthe compound listed in Column III or Table I of Examples 11 to 56, thepentaacetate ester of such compounds of Examples 11 to 56 is formed.

Examples 103 to 156

Following the procedure of Example 1 but substituting for the1-dimethylaminopropyl-3,4-dihydronaphthalene the compound set out incolumn I of Table II below, the compound set out in column II isobtained.

                                      TABLE II                                    __________________________________________________________________________    Ex.                                                                           No.                                                                              Column I                      Column II                                    __________________________________________________________________________     ##STR123##                                                                                                     ##STR124##                                     R.sub.6 (position)                                                                    m XY                  R.sub.6 (position)                                                                    m XY                                 __________________________________________________________________________    103.                                                                             H       --                                                                              N(CH.sub.3).sub.2   H       --                                                                              N(CH.sub.3).sub.2                  104.                                                                             H       --                                                                               ##STR125##         H       --                                                                               ##STR126##                        105.                                                                             H       --                                                                               ##STR127##         H       --                                                                               ##STR128##                        106.                                                                             CH.sub.3 (2)                                                                          1 (CH.sub. 2).sub.3 NHC.sub.4 H.sub.9                                                               CH.sub.3 (2)                                                                          1 (CH.sub.2).sub.3 NHC.sub.4                                                    H.sub.9                            107.                                                                              ##STR129##                                                                           1                                                                                ##STR130##                                                                                        ##STR131##                                                                           1                                                                                ##STR132##                        108.                                                                             CH.sub.3 (1) C.sub.2 H.sub.5 (2)                                                      2                                                                                ##STR133##         CH.sub.3 (1) C.sub.2 H.sub.5                                                          22)                                                                              ##STR134##                        109.                                                                             H       --                                                                              (CH.sub.2).sub.3 N(CH.sub.2 CH.sub.2 Br).sub.2                                                    H       --                                                                              (CH.sub.2).sub.3 N(CH.sub.2                                                   CH.sub.2 Br).sub.2                 110.                                                                             H       --                                                                              (CH.sub.2).sub.4 N(CH.sub.2 CH.sub.2 OH).sub.2                                                    H       --                                                                              (CH.sub.2).sub.4 N(CH.sub.2                                                   CH.sub.2 OH).sub.2                 111.                                                                             H       --                                                                              (CH.sub.2).sub.5 N(C.sub.6 H.sub.5).sub.2                                                         H       --                                                                              (CH.sub.2).sub.5 N(C.sub.6                                                    H.sub.5).sub.2                     112.                                                                             H       --                                                                               ##STR135##         H       --                                                                               ##STR136##                        113.                                                                             H       --                                                                              (CH.sub.2).sub.4 N(CH.sub.2 C.sub.6 H.sub.5).sub.2                                                H       --                                                                              (CH.sub.2).sub.4 N(CH.sub.2                                                   C.sub.6 H.sub.5).sub.2             114.                                                                             C.sub.4 H.sub.9 (2)                                                                   1 (CH.sub.2).sub.7 NH.sub.2                                                                         C.sub.4 H.sub.9 (2)                                                                   1 (CH.sub.2).sub.7 NH.sub.2          115.                                                                             CH.sub.3 (1)                                                                          1                                                                                ##STR137##         CH.sub.3 (1)                                                                          1                                                                                ##STR138##                        116.                                                                             H       --                                                                               ##STR139##         H       --                                                                               ##STR140##                        117.                                                                             H       --                                                                               ##STR141##         H       --                                                                               ##STR142##                        118.                                                                             H       --                                                                               ##STR143##         H       --                                                                               ##STR144##                        119.                                                                             H       --                                                                               ##STR145##         H       --                                                                               ##STR146##                        120.                                                                             H       --                                                                               ##STR147##         H       --                                                                               ##STR148##                         ##STR149##                                                                                                     ##STR150##                                     R.sub.6 (position)                                                                    m XY                  R.sub.6 (position)                                                                    m XY                                 __________________________________________________________________________    121.                                                                             H       --                                                                              N(CH.sub.3).sub.2   H       --                                                                              N(CH.sub.3).sub.2                  122.                                                                             H       --                                                                               ##STR151##         H       --                                                                               ##STR152##                        123.                                                                             H       --                                                                               ##STR153##         H       --                                                                               ##STR154##                        124.                                                                             CH.sub.3 (2)                                                                          1 (CH.sub.2).sub.3 NHC.sub.4 H.sub.9                                                                CH.sub.3 (2)                                                                          1 (CH.sub.2).sub.3 NHC.sub.4                                                    H.sub.9                            125.                                                                              ##STR155##                                                                           1                                                                                ##STR156##                                                                                        ##STR157##                                                                           1                                                                                ##STR158##                        126.                                                                             CH.sub.3 (1) C.sub.2 H.sub.5 (3)                                                      2                                                                                ##STR159##         CH.sub.3 (1) C.sub.2 H.sub.5                                                          23)                                                                              ##STR160##                        127.                                                                             H       --                                                                              (CH.sub.2).sub.3 N(CH.sub.2 CH.sub.2 Br).sub.2                                                    H       --                                                                              (CH.sub.2).sub.3 N(CH.sub.2                                                   CH.sub.2 Br).sub.2                 128.                                                                             H       --                                                                              (CH.sub.2).sub.4 N(CH.sub.2 CH.sub.2 OH).sub.2                                                    H       --                                                                              (CH.sub.2).sub.4 N(CH.sub.2                                                   CH.sub.2 OH).sub.2                 129.                                                                             H       --                                                                              (CH.sub.2).sub.5 N(C.sub.6 H.sub.5).sub.2                                                         H       --                                                                              (CH.sub.2).sub.5 N(C.sub.6                                                    H.sub.5).sub.2                     130.                                                                             H       --                                                                               ##STR161##         H       --                                                                               ##STR162##                        131.                                                                             H       --                                                                              (CH.sub.2).sub.4 N(CH.sub.2 C.sub.6 H.sub.5).sub.2                                                H       --                                                                              (CH.sub.2).sub.4 N(CH.sub.2                                                   C.sub.6 H.sub.5).sub.2             132.                                                                             C.sub.4 H.sub.9 (2)                                                                   1 (CH.sub.2).sub.7 NH.sub.2                                                                         C.sub.4 H.sub.9 (2)                                                                   1 (CH.sub.2).sub.7 NH.sub.2          133.                                                                             CH.sub.3 (4)                                                                          1                                                                                ##STR163##         CH.sub.3 (4)                                                                          1                                                                                ##STR164##                        134.                                                                             H       --                                                                               ##STR165##         H       --                                                                               ##STR166##                        135.                                                                             H       --                                                                               ##STR167##         H       --                                                                               ##STR168##                        136.                                                                             H       --                                                                               ##STR169##         H       --                                                                               ##STR170##                        137.                                                                             H       --                                                                               ##STR171##         H       --                                                                               ##STR172##                        138.                                                                             H       --                                                                               ##STR173##         H       --                                                                               ##STR174##                         ##STR175##                                                                                                     ##STR176##                                     R.sub.6 (position)                                                                    m XY                  R.sub.6 (position)                                                                    m XY                                 __________________________________________________________________________    139.                                                                             H       --                                                                              N(CH.sub.3).sub.2   H       --                                                                              N(CH.sub.3).sub.2                  140.                                                                             H       --                                                                               ##STR177##         H       --                                                                               ##STR178##                        141.                                                                             H       --                                                                               ##STR179##         H       --                                                                               ##STR180##                        142.                                                                             CH.sub.3 (2)                                                                          1 (CH.sub.2).sub.3 NHC.sub.4 H.sub.9                                                                CH.sub.3 (2)                                                                          1 (CH.sub.2).sub.3 NHC.sub.4                                                    H.sub.9                            143.                                                                              ##STR181##                                                                           1                                                                                ##STR182##                                                                                        ##STR183##                                                                           1                                                                                ##STR184##                        144.                                                                             CH.sub.3 (1)                                                                          2                                                                                ##STR185##         C.sub.2 H.sub.5 (2)                                                                   2                                                                                ##STR186##                        145.                                                                             H       --                                                                              (CH.sub.2).sub.3 N(CH.sub.2 CH.sub.2 Br).sub.2                                                    H       --                                                                              (CH.sub.2).sub.3 N(CH.sub.2                                                   CH.sub.2 Br).sub.2                 146.                                                                             H       --                                                                              (CH.sub.2).sub.4 N(CH.sub.2 CH.sub.2 OH).sub.2                                                    H       --                                                                              (CH.sub.2).sub.4 N(CH.sub.2                                                   CH.sub.2 OH).sub.2                 147.                                                                             H       --                                                                              (CH.sub.2).sub.5 N(C.sub.6 H.sub.5).sub.2                                                         H       --                                                                              (CH.sub.2).sub.5 N(C.sub.6                                                    H.sub.5).sub.2                     148.                                                                             H       --                                                                               ##STR187##         H       --                                                                               ##STR188##                        149.                                                                             H       --                                                                              (CH.sub.2).sub.4 N(CH.sub.2 C.sub.6 H.sub.5).sub.2                                                H       --                                                                              (CH.sub.2).sub.4 N(CH.sub.2                                                   C.sub.6 H.sub.5).sub.2             150.                                                                             C.sub.4 H.sub.9 (2)                                                                   1 (CH.sub.2).sub.7 NH.sub.2                                                                         C.sub.4 H.sub.9 (2)                                                                   1 (CH.sub.2).sub.7 NH.sub.2          151.                                                                             CH.sub.3 (4)                                                                          1                                                                                ##STR189##         CH.sub.3 (4)                                                                          1                                                                                ##STR190##                        152.                                                                             H       --                                                                               ##STR191##         H       --                                                                               ##STR192##                        153.                                                                             H       --                                                                               ##STR193##         H       --                                                                               ##STR194##                        154.                                                                             H       --                                                                               ##STR195##         H       --                                                                               ##STR196##                        155.                                                                             H       --                                                                               ##STR197##         H       --                                                                               ##STR198##                        156.                                                                             H       --                                                                               ##STR199##         H       --                                                                               ##STR200##                        __________________________________________________________________________

examples 157 to 209

Following the procedure of Example 8, but substituting for the3a,7a-trans-5,6-trans-hexahydro-1-(3-piperidinopropyl)-2,3a,5,6,7a-indanpentol,the compound listed in Column II of Table II of Examples 103 to 156, thepentaacetate ester of such compounds of Examples 103 to 156 is formed.

EXAMPLE 2102,3-trans-4a,8a-trans-5[3-(Dimethylamino)propyl]-decahydro-2,3-4a,6,7a-naphthalenepentol, 2,3,4a,8a-tetraacetate

A solution of 20 g of1,2-trans-1-[3-(dimethylamino)-propyl]-1,2,3,4,5,8-hexahydro-2-naphthol(as prepared in Example 1) in 200 ml of pyridine is treated with 10 g ofsuccinic anhydride. After standing for 1 day at 25° C, the solvent isevaporated, toluene added and evaporated, to yield the succinate halfester. This is taken up in 140 ml of glacial acetic acid and 20 ml ofacetic anhydride, cooled to 10° C in ice, and treated carefully with 7ml of 70% perchloric acid. After stirring 15 minutes, the addition of 35ml of 40% peracetic acid is carried out over 1/2 hour, at 15° C. Thetemperature is allowed to come to 25° C for 1/2 hour, then the bathtemperature is raised to 45° C for 1 hour. The mixture is then cooled to5° C and diluted with 400 ml of benzene. The upper phase is discarded,and the treatment repeated twice with benzene and twice using ethylether. The resulting viscous oil is cooled to -15° C and dissolvedcautiously in 70 ml of acetic anhydride. Another 1/2 ml of 70%perchloric is added, and after 1 day at -15° C, another 70 ml of aceticanhydride. After two more days at -15° C, the mixture is diluted with 2l. of ethyl ether and the resulting dark gum dissolved in water andrendered basic with sodium bicarbonate. This solution is extractedquickly with ethyl acetate, then the aqueous is warmed at 60°-80° C on asteam cone for 45 minutes. The resulting mixture is extracted withchloroform, dried using magnesium sulfate, and evaporated to 10 g of anoil.

Chromatography on neutral alumina, activity II, in ethyl acetate withincreasing concentrations of methanol affords a fraction containing 200mg of pure hydroxy tetraacetate, m.p. 178°-182° C.

EXAMPLE 2112,3-trans-4a,8a-trans-5-[3-(Dimethylamino)propyl]-decahydro-2,3,4a,6,8a-naphthalenepentol, pentamethyl ether

A mixture of the pentol as prepared in Example 1, 0.01 mole, in 100 mlof dimethyl formamide is treated with 0.05 mole of sodium hydride (50%dispersion in mineral oil) and heated at 40° C for 1/2 hours, untilhydrogen evolution has ceased. To this mixture is added 0.05 mole ofmethyl iodide over 1/2 hour, maintaining the temperature at 35°-40° C.After the addition is complete, heating is continued for 2 hours, thenthe mixture is cooled and treated cautiously with water to decomposeexcess hydride. The resulting mixture is diluted with 200 ml of waterand extracted with ethyl acetate. The dried organic phase is filteredand the hydrochloride salt of the pentamethyl ether precipitated by theaddition of a saturated solution of hydrogen chloride in isopropanol.

EXAMPLE 212

The penta (chloro propyl) ether of the compound of Example 1 is preparedby substituting 1-bromo-3-chloropropane for methyl iodide in Example211.

EXAMPLE 213

The penta (ethyl carbonate) of the compound of Example 1 is prepared bysubstituting ethyl chloro formate for methyl iodide in Example 211.

EXAMPLE 214

The penta (dimethyl carbamate) of the compound of Example 1 is preparedby substituting dimethyl carbamyl chloride for methyl iodide in Example211.

EXAMPLE 215

The penta (ethoxy ethyl) ether of the compound of Example 1 is preparedby substituting 2-ethoxy ethyl bromide for methyl iodide in Example 211.

What is claimed is:
 1. A compound of the structure ##STR201## whereinR₁, R₂, R₃, R₄ and R₅ are the same or different and are selected fromthe group consisting of hydrogen, lower alkyl, trifluoromethyl,mono-halo-lower alkyl wherein the halogen is F, Cl, Br or I, acylradical of a hydrocarbon carboxylic acid of less than 12 carbon atoms,amido, lower alkoxyalkylene and lower alkoxy carbonyl, X is a singlebond or a straight or branched chain alkylene group of the structure(CH₂)_(n') wherein n' is 0 to 10, Y is ##STR202## wherein R₇ and R₈ arethe same or different and are selected from the group consisting ofhydrogen, lower alkyl, trifluoromethyl, monocyclic cycloalkyl having 3to 6 ring members, monocyclic cycloalkyl lower alkyl, wherein thecycloalkyl has 3 to 6 ring members, hydroxy-lower alkyl, phenyl, loweralkylphenyl, acyl radical of a hydrocarbon carboxylic acid of less than12 carbon atoms, di(lower alkyl)phenyl, halophenyl, mono-, di- ortri-nitrophenyl, phenyl lower alkyl, monocyclic heterocyclic, whereinlower alkyl contains 1 to 8 carbons, R₆ is lower alkyl or cycloalkylhaving 3 to 6 ring members, and ##STR203## can be taken together to forma heterocyclic radical; wherein the heterocyclic radicals represented byR₇, R₈ or ##STR204## taken together contain 5-, 6- or 7-members in theheterocyclic ring, the ring being pyrrolidine, piperidine, morpholine,thiamorpholine, piperazine or homopiperazine provided that one of saidrings is always present, and n is 1 to 3; m is 0, 1 or 2; stereoisomersthereof, physiologically acceptable acid salts thereof, physiologicallyacceptable quaternary salts thereof and N-oxides thereof.
 2. A compoundaccording to claim 1 wherein R₁, R₂, R₃, and R₄ are hydrogen or alkanoylof 1 to 3 carbons.
 3. A compound according to claim 2 wherein R₁, R₂,R₃, R₄ and R₅ are alkanoyl.
 4. A compound according to claim 2 whereinR₁, R₂, R₃ and R₄ are acetyl.
 5. A compond according to claim 2 whereinR₁, R₂, R₃, R₄ and R₅ are acetyl.
 6. A compound according to claim 1having the structure ##STR205## wherein n' is zero to ten and R₆ islower alkyl or cycloalkyl containing from 3 to 6 ring members, m is 0, 1or 2, and stereoisomers thereof.
 7. A compound according to claim 1having the structure ##STR206## wherein n' is zero to ten and R₆ islower alkyl or cycloalkyl containing from 3 to 6 ring members, m is 0, 1or 2, R₁, R₂, R₃, R₄ and R₅ are acetyl and stereoisomers thereof.
 8. Acompound according to claim 1 wherein R₁, R₂, R₃, and R₄ are loweralkyl, halo-lower alkyl, or lower alkoxyalkylene.
 9. A compoundaccording to claim 1 wherein R₁, R₂, R₃, R₄ and R₅ are amido.
 10. Acompound according to claim 1 wherein R₁, R₂, R₃, R₄ and R₅ are loweralkoxy carbonyl.
 11. A compound according to claim 1 having thestructure ##STR207##
 12. A compound according to claim 1 having thestructure ##STR208##
 13. A compound according to claim 1 having thestructure ##STR209##
 14. A compound according to claim 1 having thestructure ##STR210##
 15. A compound according to claim 1 having thestructure ##STR211##
 16. A compound according to claim 1 wherein R₅ is Hand R₁, R₂, R₃ and R₄ are lower alkanoyl.
 17. A hypertensive compositioncomprising an effective amount of compound as defined in claim 1 and apharmaceutically acceptable carrier thereof.
 18. A method of treatinghypertension in mammalian species, which comprises administering to amammalian host a therapeutic amount of the composition as defined inclaim 17.